Trial of VQ-101 for patients with GBA gene mutations begins dosing

1st patient dosed in first-in-human study of oral Parkinson's therapy

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by Andrea Lobo |

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The term 'clinical trials' with a handful of oral medications above it and a heart rate graph below it.

The first patient has been dosed in a first-in-human trial testing Vanqua Bio’s VQ-101 as an oral therapy for Parkinson’s disease linked to mutations in the GBA gene, the company has announced.

The Phase 1 clinical trial is assessing the safety, tolerability, and pharmacological properties of VQ-101 in both healthy volunteers and Parkinson’s patients with or without GBA gene mutations, according to a company press release.

The participants will be randomly assigned to receive either the experimental therapy, at single or multiple ascending doses, or a placebo. Vanqua Bio last year announced VQ-101 was advancing to clinical development after positive results in studies in the lab.

“VQ-101 demonstrated promising efficacy, safety, pharmacokinetics [pharmacological properties], and target engagement in preclinical studies,” said Jim Sullivan, PhD, Vanqua Bio’s CEO.

“This evolution to a clinical-stage company is an important milestone for Vanqua and brings us closer to our goal of addressing unmet patient needs through evidence-based innovation,” Sullivan added.

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GBA gene mutations among the most common genetic causes of Parkinson’s

Parkinson’s is caused by the progressive dysfunction and death of dopaminergic neurons, a type of nerve cell responsible for producing the chemical messenger dopamine.

Mutations in the GBA gene are one of the most common genetic causes of Parkinson’s disease. This gene encodes an enzyme called glucocerebrosidase, known as GCase, that helps break down the fatty molecule glucocerebroside inside lysosomes, which are cells’ recycling compartments.

These mutations lead to a reduction of GCase activity, impairing lysosomal function. As a result, toxic forms of proteins, including alpha-synuclein, accumulate into clumps inside nerve cells. Accumulation of such toxic protein clumps, particularly those composed of alpha-synuclein, is a Parkinson’s hallmark.

VQ-101 is a brain-penetrant small molecule that acts as an allosteric activator of the GCase enzyme, meaning it binds to and increases the enzyme’s activity. Therefore, the treatment is expected to restore lysosomal function, preventing the accumulation of alpha-synuclein and resultant nerve cell damage.

No details have been given on the number of participants the study will enroll or where it will be held.

The Phase 1 trial launch was grounded on positive findings from preclinical studies showing VQ-101 was safe and well tolerated, and increased GCase activity, while decreasing the accumulation of alpha-synuclein clumps.

Specifically, VQ-101 was shown to bind and increase the activity of GCase in dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) derived from Parkinson’s patients with GBA mutations. iPSCs are derived from adult cells, reprogrammed back into a stem cell-like state, and able to differentiate in almost any cell type.

Moreover, it reduced the accumulation of GCase substrates, such as glucocerebroside, and significantly reduced the accumulation of alpha-synuclein clumps. Activation of GCase by VQ-101 was confirmed in blood samples obtained from healthy volunteers and people with GBA-linked Parkinson’s disease.

In animal models across four species, once-daily oral administration of VQ-101 was shown to enhance GCase activity, in a dose and time-dependent manner.

The company also shared data from an assay it developed to assess GCase activity in both human and animal models’ blood samples. According to the Vanqua, the assay will be used to assess GCase activation in the Phase 1 trial.

“The launch of the Phase 1 study exemplifies Vanqua Bio’s ability to translate our lysosomal biology and medicinal chemistry expertise into pioneering treatments that are well suited for clinical development,” Sullivan said.